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BACKGROUND AND AIMS: Non-invasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a non-invasive algorithm for the prediction of varices in patients with unresectable HCC. METHODS: We performed a retrospective cohort study in 21 centers in the US including adult patients with unresectable HCC and Child Pugh A5-B7 cirrhosis diagnosed between 2007 and2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but prior to HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients. RESULTS: We included 707 patients (median age 64.6 years, 80.6% male and 74.0% White). Median time from HCC diagnosis to EGD was 47 (IQR: 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved a NPV of 86.3% in the validation cohort, while a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in over half of low-risk patients while misclassifying 7.7% of high-risk patients. CONCLUSION: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients prior to the initiation of systemic therapy, thus expediting their care and avoiding treatment delays.
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PURPOSE: To characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. MATERIALS AND METHODS: With Institutional Animal Care and Use Committee (IACUC) approval, 11 female swine underwent either right (n = 5) or left (n = 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound (US)-guided MWA was performed in each liver segment (left lateral, left medial, right medial, and right lateral) at either 30 W (n = 4 lobes), 60 W (n = 4), 65 W (n = 20), 90 W (n = 8), 120 W (n = 4), or 140 W (n = 4) continuously for 5 minutes. Postprocedural volumetric segmentation was performed on standardized multiphase T1 magnetic resonance (MR) imaging sequences. RESULTS: Mean AZVs in embolized lobes (15.8 mL ± SD 10.6) were significantly larger than those in nonembolized lobes (11.2 mL ± SD 6.5, P < .01). MWA energy demonstrated significant positive linear correlation with both embolized (R2 = 0.66, P < .01) and nonembolized (R2 = 0.64, P < .01) lobes. The slope of the linear models corresponded to a 0.95 mL/kJ (SD ± 0.16) and 0.54 mL/kJ (SD ± 0.09) increase in ablation volume per applied kilojoule of energy (E) in embolized and nonembolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the following interaction term: 0.42∗E∗(embolization status) (P = .031). CONCLUSIONS: Linear models demonstrated a near 1.8-fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to nonembolized lobes. Absolute AZV differences between embolized and nonembolized lobes were greater at higher-power MWA.
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Embolización Terapéutica , Arteria Hepática , Hígado , Microondas , Modelos Animales , Animales , Microondas/uso terapéutico , Femenino , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Arteria Hepática/diagnóstico por imagen , Porcinos , Técnicas de Ablación , Sus scrofa , Imagen por Resonancia Magnética , Ultrasonografía IntervencionalRESUMEN
PURPOSE: The objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume. MATERIALS AND METHODS: PK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe. RESULTS: Microwave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (Ktrans = 0.69 min-1 ± 0.15 vs 1.52 min-1 ± 0.37, P < .001; kep = 0.69 min-1 ± 0.19 vs 1.54 min-1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized kep and ablation volume, with each unit increase in normalized kep corresponding to a 9.8-mL decrease in ablation volume (P = .035). CONCLUSIONS: PK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.
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Embolización Terapéutica , Hígado , Porcinos , Animales , Hígado/diagnóstico por imagen , Hígado/cirugía , Hígado/patología , Imagen por Resonancia Magnética/métodos , Perfusión , Embolización Terapéutica/efectos adversosRESUMEN
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
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Várices Esofágicas y Gástricas , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Ascitis/etiología , Várices Esofágicas y Gástricas/complicaciones , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/cirugía , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid adjacent major structure injury. The aim of this study was to sequentially evaluate the effects of IRE on the femoral nerve during acute-to-delayed periods in a rabbit model. MATERIAL AND METHODS: Ultrasound-guided IRE of femoral neurovascular bundles was performed in seven rabbits. Functional and histopathologic evaluation was performed sequentially after IRE. The extent of nerve fiber affected, and the proportion of perineurial inflammation and surrounding tissue injury were recorded. RESULTS: After IRE, femoral nerve function was damaged before four weeks, but then gradually returned to normal. Perineural inflammatory cell infiltration was most severe three days after IRE (80-85%), and was normalized after eight weeks. Surrounding tissue injury was prominent at three days and one week after IRE (80-90%), and then gradually recovered. However, peripheral nerve fibers were markedly damaged at one and two weeks (80-100%). Nerve fibers then recovered and were normalized at eight weeks. CONCLUSION: Nerve tissue injury with transient functional impairment can occur after IRE. However, endoneurial and epineurial extracellular matrix were preserved with Schwann cell regeneration, which could lead to regeneration of nerve tissues within eight weeks.
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Técnicas de Ablación , Electroporación , Animales , Nervio Femoral , Conejos , UltrasonografíaRESUMEN
There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.
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Técnicas de Ablación/métodos , Neoplasias/cirugía , Consenso , Humanos , Reproducibilidad de los Resultados , Sociedades MédicasRESUMEN
PURPOSE: To characterize the effect of hepatic vessel flow using 4-dimensional (4D) flow magnetic resonance (MR) imaging and correlate their effect on microwave ablation volumes in an in vivo non-cirrhotic porcine liver model. MATERIALS AND METHODS: Microwave ablation antennas were placed under ultrasound guidance in each liver lobe of swine (n = 3 in each animal) for a total of 9 ablations. Pre- and post-ablation 4D flow MR imaging was acquired to quantify flow changes in the hepatic vasculature. Flow measurements, along with encompassed vessel size and vessel-antenna spacing, were then correlated with final ablation volume from segmented MR images. RESULTS: The linear regression model demonstrated that the preablation measurement of encompassed hepatic vein size (ß = -0.80 ± 0.25, 95% confidence interval [CI] -1.15 to -0.22; P = .02) was significantly correlated to final ablation zone volume. The addition of hepatic vein flow rate found via 4D flow MRI (ß = -0.83 ± 0.65, 95% CI -2.50 to 0.84; P = .26), and distance from antenna to hepatic vein (ß = 0.26 ± 0.26, 95% CI -0.40 to 0.92; P = .36) improved the model accuracy but not significantly so (multivariate adjusted R2 = 0.70 vs univariate (vessel size) adjusted R2 = 0.63, P = .24). CONCLUSIONS: Hepatic vein size in an encompassed ablation zone was found to be significantly correlated with final ablation zone volume. Although the univariate 4D flow MR imaging-acquired measurements alone were not found to be statistically significant, its addition to hepatic vein size improved the accuracy of the ablation volume regression model. Pre-ablation 4D flow MR imaging of the liver may assist in prospectively optimizing thermal ablation treatment.
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Técnicas de Ablación , Venas Hepáticas/diagnóstico por imagen , Circulación Hepática , Hígado/irrigación sanguínea , Hígado/cirugía , Imagen por Resonancia Cinemagnética , Microondas , Imagen de Perfusión/métodos , Animales , Velocidad del Flujo Sanguíneo , Estudios de Factibilidad , Venas Hepáticas/fisiopatología , Modelos Animales , Valor Predictivo de las Pruebas , Sus scrofaRESUMEN
OBJECTIVES: The purpose of this study was to describe a single institution's experience with transradial access (TRA) for angiographic interventions, and to compare technical success, complication rate and radiation dose of procedures performed with TRA to those performed with transfemoral access (TFA). METHODS: A retrospective cohort study of patients undergoing peripheral interventions via TRA or TFA from 2015 to 2017 was performed. The cohort comprised 33 patients undergoing 44 procedures via TRA and 37 patients undergoing 44 procedures via TFA. Outcome measures were technical success, access-related complications, fluoroscopy time and radiation exposure. Differences at p < 0.05 were considered to be statistically significant. RESULTS: Baseline characteristics were similar between patients who had procedures via TRA versus those who had procedures via TFA, including age, sex and body mass index. Technical success was achieved in 41/44 (93.2%) of procedures performed via TRA, compared to 44/44 (100%) of procedures performed via TFA (p = 0.241). There were three access-related complications (6.8%) when TRA was performed, compared to none when TFA was performed (p = 0.241). Fluoroscopy time was longer in procedures performed with TRA compared to those performed with TFA (27.3 vs 20.4, p = 0.033). Dose area product (DAP) did not differ with access site choice (p = 0.186). CONCLUSIONS: TRA is a safe and feasible alternative to TFA for a range of peripheral interventions. However, TRA must be performed with prudence as it is not without complications and is technically challenging, leading to longer fluoroscopy time. KEY POINTS: ⢠Transradial access (TRA) is feasible in a variety of peripheral interventions, achieving success in 93.2% of cases. ⢠Access-related complications are comparable between transfemoral access (TFA) and TRA (p = 0.241), but prudence must be taken during TRA as it could be technically challenging. ⢠Procedures performed with TRA tend to have longer fluoroscopy time compared to those performed with TFA (p = 0.033), but the DAPs are comparable (p = 0.186).
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Angiografía/métodos , Cateterismo Periférico/métodos , Exposición a la Radiación/efectos adversos , Angiografía/efectos adversos , Estudios de Factibilidad , Femenino , Arteria Femoral , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Arteria Radial , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: To compare age-related morbidity and mortality after transjugular intrahepatic portosystemic shunts (TIPS). METHODS: We performed a retrospective chart review of patients who underwent TIPS at the University of California Los Angeles Medical Center between 2008 to 2014. Elderly patients (65 y and older) were matched with nonelderly patients (controls, below 65 y) by model for end-stage liver disease (MELD) score (±3), indication for TIPS (refractory ascites vs. variceal bleeding), serum sodium level (±5), in a ratio of 1:1. Endpoints measures were hospital stay post-TIPS, rifaximin, or lactulose use, TIPS failure at 30 days, readmission at 90 days, MELD at 90 days, and mortality at 90 days. RESULTS: A total of 30 patient matches were included in this study: 30 control and 30 elderly patients. The median [interquartile (IQR)] MELD scores for controls and elderly were 11 (9, 13.8) for the controls and 11.5 (9, 14.8) for elderly patients (P=0.139). There were no significant differences in serum sodium and indication for TIPS. Thirty and 90-day follow-up laboratory test results were also similar between elderly and control patients. Event-free survival at 90 days was similar between controls and elderly patients [odds ratio (OR), 0.86; 95% confidence interval (CI), 0.3-2.5; P>0.05]. There was a trend toward greater hospitalization (OR, 1.76; 95% CI, 0.52-5.95; P=0.546) and mortality (OR, 3.3; 95% CI, 0.3-14.01; P=0.182). CONCLUSIONS: The results of this study suggest event-free survival is similar between nonelderly and elderly patients. Although statistically significant, there is a tendency toward greater mortality and hospitalization in the elderly.
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Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular/mortalidad , Factores de Edad , Anciano , California , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND STUDY AIMS: We evaluated the efficacy of small interfering RNA (siRNA) in targeting matrix metalloproteinase (MMP-9) to suppress stent-induced tissue hyperplasia in a rat esophageal model. METHODS: The silencing effect of the candidate siRNA (termed (MMP-9 siRNA) was evaluated in 9âL rat glial cells. Four groups of rats (nâ=â10, each group) were used: Eso-S, stent insertion only, comparison; Eso-R, stent insertion plus treatment with MMP-9 siRNA complexed with Chol-R9 for delivery, experimental; Eso-P, stent insertion plus treatment with pCMV-luc complexed with Chol-R9, for confirmation of Chol-R9 delivery effect; and Eso-N, no stent insertion and no treatment, controls. All rats were sacrificed at 3 weeks. The therapeutic efficacy of the MMP-9 siRNA/Chol-R9 complex was assessed. RESULTS: The most potent MMP-9 siRNA was selected. Compared with the Eso-S group, the Eso-R group showed significantly less tissue hyperplasia with a lower percentage of granulation tissue and smaller granulation tissue area, and also significantly lower MMP-9 level. CONCLUSIONS: MMP-9 siRNA/Chol-R9 is effective for inhibiting stent-induced tissue hyperplasia in a rat esophageal model.
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Esófago/patología , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Stents/efectos adversos , Animales , Células Cultivadas , Colesterol/análogos & derivados , Sistemas de Liberación de Medicamentos , Enoxacino/farmacología , Hiperplasia/enzimología , Hiperplasia/etiología , Hiperplasia/prevención & control , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Neuroglía/efectos de los fármacos , Oligopéptidos , ARN Interferente Pequeño/farmacología , Ratas , Ratas Sprague-Dawley , Inhibidores de Topoisomerasa II/farmacología , TransfecciónRESUMEN
PURPOSE: To investigate the success and safety of routine versus advanced inferior vena cava (IVC) filter retrieval techniques. MATERIALS AND METHODS: A retrospective review was performed of patients who underwent IVC filter placement and/or a retrieval attempt over a 10-year period. Retrieval technique(s), preretrieval computed tomography, preretrieval venography, and clinical/imaging follow-up for 30 days after retrieval were analyzed. Mean filter dwell time was 134 days (range, 0-2,475 d). RESULTS: Filter retrieval was attempted 231 times in 217 patients (39% female, 61% male; mean age, 50.7 y), with success rates of 73.2% (169 of 231) and 94.7% (54 of 57) for routine and advanced filter retrieval techniques, respectively. The overall filter retrieval complication rate was 1.7% (four of 231); complications in four patients (with multiple complications in some cases) included IVC dissection, IVC intussusception, IVC thrombus/stenosis, filter fracture with embedded strut, IVC injury with hemorrhage, and vascular injury from complicated venous access. The rate of complications associated with filter retrievals that required advanced technique was significantly higher than seen with routine technique (5.3% vs 0.4%; P < .05). Longer dwell time, more transverse tilt, and presence of an embedded hook were associated with significantly increased rates of failed retrieval via routine technique (P < .05). CONCLUSIONS: IVC filters can be retrieved with a high overall success rate (98.2%) and a low complication rate (1.7%) by using advanced techniques when the routine approach has failed; however, the use of advanced techniques is associated with a significantly higher complication rate.
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Remoción de Dispositivos/métodos , Procedimientos Endovasculares , Implantación de Prótesis/instrumentación , Filtros de Vena Cava , Vena Cava Inferior , Remoción de Dispositivos/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Flebografía/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vena Cava Inferior/diagnóstico por imagenRESUMEN
The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.
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Dieta , Neuropéptido Y/genética , Obesidad/metabolismo , Estrés Fisiológico/metabolismo , Células 3T3-L1 , Tejido Adiposo Blanco/metabolismo , Animales , Frío , Grasas de la Dieta , Eliminación de Gen , Regulación de la Expresión Génica , Masculino , Síndrome Metabólico , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Neuropéptido Y/metabolismo , Receptores de Neuropéptido Y/genética , Regulación hacia ArribaRESUMEN
A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8), were further suppressed by a single ip injection of a Treg-depleting mAb given 2 days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result: The median (days) [SD/total N] of survival went from 15[1.09/62] (no treatment control) to 35.8[8.8/58] (radiation therapy only) to 52.5[13.5/57] (radiation therapy plus immunotherapy). Within 2 weeks after immunization, tumors in mice receiving radiation therapy plus immunotherapy were significantly smaller than tumors in mice treated only with radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon γ production when cultured with syngeneic tumor cells. We suggest that our model will be useful for the development and testing of novel combination therapies for brain tumors.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias Encefálicas/terapia , Melanoma Experimental/terapia , Animales , Anticuerpos Monoclonales/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/radioterapia , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Terapia Combinada , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Inmunoterapia , Interferón gamma/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/radioterapia , Ratones , Ratones Endogámicos C57BLRESUMEN
PURPOSE: To investigate the efficacy of an IN-1233-eluting covered stent in preventing tissue hyperplasia in a rabbit esophageal model. MATERIALS AND METHODS: The local animal research committee approved all experiments. Esophageal stents were placed in 40 male New Zealand rabbits (weight range, 2.8-3.2 kg). The drug group (D) received IN-1233-eluting covered stents (n = 20); the control group (C) received polyurethane-covered stents (n = 20). Drug loading of IN-1233-eluting covered stent was 10%. Four study groups were formed: C and D animals sacrificed at 4 (D4, C4) and 8 (D8, C8) weeks after stent placement (n = 10). Esophagography was used to assess the percentage of diameter stenosis. Histologic findings of the drug and control stents were compared. The Mann-Whitney U test was used to evaluate differences. RESULTS: The mean percentage ± standard deviation of diameter stenosis was significantly lower in D groups than in C groups at both 4 (C4 = 36.15% ± 12.63, D4 = 7.83% ± 8.12 [P < .001]) and 8 (C8 = 50.21% ± 20.43, D8 = 27.78% ± 14.40 [P = .019]) weeks. Percentage of granulation tissue area (C4 = 33.07% ± 19.11, D4 = 21.59% ± 18.22 [P = .028]; C8 = 44.70% ± 21.71, D8 = 31.97% ± 22.54 [P = .131]), number of epithelial layers (C4 = 4.77 ± 1.55, D4 = 3.37 ± 1.73 [P = .002]; C8 = 5.50 ± 1.38, D8 = 4.50 ± 1.63 [P = .057]), and thickness of submucosal fibrosis (C4 = 2.42 mm ± 1.08, D4 = 1.62 mm ± 0.77 [P = .006]; C8 = 2.89 mm ± 1.00, D8 = 2.07 mm ± 0.71 [P = .007]) were lower in D than in C groups. Inflammatory cell infiltration was significantly higher in D than in C groups (C4 = 2.63 ± 0.81, D4 = 3.33 ± 1.09 [P = .032]; C8 = 2.20 ± 0.81, D8 = 3.00 ± 0.95 [P = .012]). CONCLUSION: The use of an IN-1233-eluting covered stents decreased tissue hyperplasia secondary to stent placement in a rabbit esophageal model.
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Benzamidas/farmacología , Stents Liberadores de Fármacos , Esófago/patología , Quinolinas/farmacología , Animales , Benzamidas/administración & dosificación , Esófago/diagnóstico por imagen , Hiperplasia/patología , Masculino , Metales , Poliuretanos , Quinolinas/administración & dosificación , Conejos , Radiografía , Estadísticas no ParamétricasRESUMEN
Gastrointestinal (GI) cancers are among the leading causes of cancer-related mortality and have traditionally been treated using a combination of surgical resection and chemoradiotherapy (CRT). While the introduction of immunotherapies over the last decade have dramatically changed the treatment landscape for some GI malignancies, including esophageal, gastric, and colorectal cancer, treatment resistance remains a major unaddressed obstacle for many patients. There has thus been emerging interest in determining the optimal treatment strategy for the delivery of immunotherapy in combination with traditional therapies. In this regard, a growing number of preclinical and clinical studies have suggested that combining radiation therapy (RT) with immunotherapy may work synergistically to improve treatment response through amplification of the abscopal effect. In this review, we discuss the rationale for RT in combination with immunotherapy. We further discuss how this knowledge may lead to a paradigm shift in the application of RT and highlight remaining issues pertaining to the delivery of combination therapy.
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PURPOSE: To demonstrate, evaluate, and verify the existence of irreversible electroporation (IRE)-ablation induced nanopores on the plasma membrane of hepatocytes. MATERIALS AND METHODS: On animal research committee approval, four New Zealand rabbits and two Yorkshire swine underwent IRE ablation of the liver (90 pulses, 100 µs per pulse at 2,500 V), and selected ablated liver tissues were harvested, fixed, and air-dried according to the electron microscopy (EM) protocol. A scanning electron microscope (SEM; Nova 230 NanoSEM [FEI, Hillsboro, Oregon] with 80 picoamperes and 10-kV acceleration) was used to visualize and verify IRE-created nanopores. Using NIH image (Bethesda, Maryland) and ImageScope (Aperio Inc., Vista, California), 21 ablated tissues (16 rabbit, 5 swine) were evaluated. Corresponding hematoxylin and eosin (H&E) evaluation was performed to verify IRE-induced cell death. RESULTS: In all 21 IRE-ablated tissues, the SEM was able to show numerous, well-circumscribed, round, and concave-shaped pore defects disturbing the hepatocyte plasma membranes. These pores were not seen in normal liver. The size of the nanopores ranged from 80-490 nm with the greatest frequency of pores in bimodal distribution. The highest frequency of pore size was noted at the size range 340-360 nm. CONCLUSIONS: IRE induces nanopores on hepatocyte membranes, as shown by SEM. The pore diameters are larger than nanopores created by reversible electroporation (RE), which may have implications for irreversibility or permanency.
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Electroporación/métodos , Hepatocitos/ultraestructura , Hígado/cirugía , Animales , Membrana Celular/ultraestructura , Hígado/citología , Microscopía Electrónica de Rastreo , Nanoporos/ultraestructura , Conejos , PorcinosRESUMEN
PURPOSE: To show the effectiveness and safety of irreversible electroporation (IRE) in treating large tumor models. MATERIALS AND METHODS: VX2 liver tumor implantation was performed in 35 New Zealand White Rabbits. The rabbits were divided into three groups 1 week after implantation. The control group included 15 rabbits; the remaining 20 rabbits were divided into two IRE treatment groups. For the treatment groups, 10 rabbits underwent ablation with a single IRE application (IRE-S group), and 10 rabbits underwent ablation with multiple IRE applications (IRE-M group). Treatments and outcomes were analyzed using ultrasound, contrast-enhanced computed tomography (CT), and immunohistologic staining (hematoxylin and eosin [H&E], P-53, Ki-67, CD30, and vascular endothelial growth factor receptor [VEGFR] staining, and terminal deoxynucleotidyl-transferase-mediated 2'-deoxyuridine 5'-triphosphate [dUTP]-biotin nick-end labeling [TUNEL] assay). RESULTS: Multiple IRE ablations consistently produced complete cell death in all the animals in the IRE-M group (n = 10, IRE ablation time 2.45 minutes ± 0.3). The results were validated with ultrasound, CT, H&E, Ki-67, P53, and TUNEL assay. A high level of CD30-positive cells were identified in the IRE groups. A sharply demarcated ablation zone with no damage to surrounding vital structures was observed in all IRE-treated tissues. No complications during or after ablation were observed in any of the animals. CONCLUSIONS: The effects of IRE were shown in a large tumor model with single and multiple IRE ablations (IRE-S and IRE-M treatment groups); complete ablation of the tumor was seen in the IRE-M group. These findings successfully show the beneficial effects and safety of IRE in the treatment of tumors and validate its potential as a clinically translatable treatment.
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Técnicas de Ablación , Electroporación , Neoplasias Hepáticas/cirugía , Animales , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Medios de Contraste , Estudios de Factibilidad , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Conejos , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Proteína p53 Supresora de Tumor/metabolismo , UltrasonografíaRESUMEN
OBJECTIVE: The objective of our study was to determine whether vascular enhancement and image quality can be preserved in pulmonary CT angiography (CTA) performed on a 64-MDCT scanner with 30 mL of IV contrast material. MATERIALS AND METHODS: This retrospective matched-cohort study compared image quality of pulmonary CTA performed using 30 mL of IV contrast material versus 100 mL of IV contrast material. CT images of 50 patients (46 men, four women; mean age, 66 years) who underwent pulmonary CTA on a 64-MDCT scanner using a low dose (30 mL) of iodixanol 320 and another 50 patients (49 men, one woman; mean age, 65 years) who underwent pulmonary CTA using a regular dose (100 mL) of contrast material during the same time period were selected for review. The 30- and 100-mL pulmonary CTA studies were retrospectively evaluated by two thoracic radiologists in random order. Attenuation values were recorded over the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries. Image quality was also subjectively assessed using visual scores on a scale from 1 (nondiagnostic) to 5 (excellent). RESULTS: The average attenuation measurements of the main, right main, selected lobar, segmental, and subsegmental pulmonary arteries were 260, 262, 280, 316, and 338 HU, respectively, on the 30-mL studies and 313, 301, 316, 344, and 349 HU, respectively, on the 100-mL studies. The average visual score was 4.0 for both the 30- and 100-mL groups. A visual score of 4 or 5 was given to 82% of studies in the 30-mL group and 78% of studies in the 100-mL group. CONCLUSION: Contrast agent dose for pulmonary CTA using a 64-MDCT scanner can be significantly reduced without compromising diagnostic image quality.
Asunto(s)
Angiografía/métodos , Medios de Contraste/administración & dosificación , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Ácidos Triyodobenzoicos/administración & dosificación , Anciano , Algoritmos , Femenino , Humanos , Masculino , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: To evaluate the techniques, efficacy, and safety for treating vascularly inaccessible abdominal visceral pseudoaneurysms by direct puncture and embolization. METHODS: A retrospective study of 5 consecutive patients who underwent percutaneous direct puncture embolization for intra-abdominal pseudoaneurysms in our institution between January 2009 and December 2016. Technical aspects, success, clinical outcome, and complications were discussed. RESULTS: Four patients (80%) were men, and the mean age of all five patients was 57.2 years (range, 47-72 years). The mean diameter of the pseudoaneurysms was 2.5 cm (range, 1.9-3.4 cm). All the pseudoaneurysms were punctured under the imaging guidance of fluoroscopy, ultrasound, or computed tomography. Coils and glue were used in four of the patients, the remaining one with coil only. The mean injected glue volume was 1.5 (range, 0.8-2) mL. The overall technical and clinical success rate was 100% without major complications or mortality. CONCLUSION: Our single-center experience and the literature review demonstrate that percutaneous direct puncture embolization is feasible and effective to serve as an alternative for treating abdominal vascular pseudoaneurysms when the traditional endovascular embolization fails. In this approach, fluoroscopy is the most needed guidance technique.